Combinatorial evaluation of in vivo distribution of polyanhydride particle-based platforms for vaccine delivery

Latrisha K Petersen,¹ Lucas Huntimer,² Katharine Walz,¹ Amanda Ramer-Tait,² Michael J Wannemuehler,² Balaji Narasimhan<sup>1

1</sup>Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, USA; ²Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA

Abstract: Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All nanoparticles rapidly dispersed when delivered intranasally but provided a depot when administered parenterally. When amphiphilic and hydrophobic nanoparticles were administered intranasally, they persisted within lung tissue. These results provide insights into the chemistry- and route-dependent distribution and tissue-specific association of polyanhydride nanoparticle-based vaccine adjuvants.

Keywords: combinatorial, polyanhydride, nanoparticle, live animal imaging, distribution